In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke

Abstract The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and flu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Himanshu Shekhar, Robert T. Kleven, Tao Peng, Arunkumar Palaniappan, Kunal B. Karani, Shaoling Huang, David D. McPherson, Christy K. Holland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d1579c4e74a347bc8589b30a95b120f9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d1579c4e74a347bc8589b30a95b120f9
record_format	dspace
spelling	oai:doaj.org-article:d1579c4e74a347bc8589b30a95b120f92021-12-02T15:09:20ZIn vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke10.1038/s41598-019-46112-z2045-2322https://doaj.org/article/d1579c4e74a347bc8589b30a95b120f92019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46112-zhttps://doaj.org/toc/2045-2322Abstract The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized using an inverted microscope. The perfusate consisted of either (1) plasma alone, (2) rt-PA, (3) OFP t-ELIP, (4) rt-PA and US, (5) OFP t-ELIP and US, (6) Definity and US, or (7) rt-PA, Definity, and US (n = 16 clots per group). An intermittent US insonation scheme was employed (220 kHz frequency, and 0.44 MPa peak-to-peak pressures) for 30 min. Microscopic imaging revealed that OFP t-ELIP included a variety of structures such as liposomes (with and without gas) and lipid-shelled microbubbles. OFP t-ELIP preserved up to 76% of rt-PA activity in the presence of PAI-1, whereas only 24% activity was preserved for unencapsulated rt-PA. The use of US with rt-PA and Definity enhanced lytic efficacy (p < 0.05) relative to rt-PA alone. US combined with OFP t-ELIP enhanced lysis over OFP t-ELIP alone (p < 0.01). These results demonstrate that ultrasound combined with Definity or OFP t-ELIP can enhance the lytic activity relative to rt-PA or OFP t-ELIP alone, respectively.Himanshu ShekharRobert T. KlevenTao PengArunkumar PalaniappanKunal B. KaraniShaoling HuangDavid D. McPhersonChristy K. HollandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Himanshu Shekhar Robert T. Kleven Tao Peng Arunkumar Palaniappan Kunal B. Karani Shaoling Huang David D. McPherson Christy K. Holland In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke
description	Abstract The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized using an inverted microscope. The perfusate consisted of either (1) plasma alone, (2) rt-PA, (3) OFP t-ELIP, (4) rt-PA and US, (5) OFP t-ELIP and US, (6) Definity and US, or (7) rt-PA, Definity, and US (n = 16 clots per group). An intermittent US insonation scheme was employed (220 kHz frequency, and 0.44 MPa peak-to-peak pressures) for 30 min. Microscopic imaging revealed that OFP t-ELIP included a variety of structures such as liposomes (with and without gas) and lipid-shelled microbubbles. OFP t-ELIP preserved up to 76% of rt-PA activity in the presence of PAI-1, whereas only 24% activity was preserved for unencapsulated rt-PA. The use of US with rt-PA and Definity enhanced lytic efficacy (p < 0.05) relative to rt-PA alone. US combined with OFP t-ELIP enhanced lysis over OFP t-ELIP alone (p < 0.01). These results demonstrate that ultrasound combined with Definity or OFP t-ELIP can enhance the lytic activity relative to rt-PA or OFP t-ELIP alone, respectively.
format	article
author	Himanshu Shekhar Robert T. Kleven Tao Peng Arunkumar Palaniappan Kunal B. Karani Shaoling Huang David D. McPherson Christy K. Holland
author_facet	Himanshu Shekhar Robert T. Kleven Tao Peng Arunkumar Palaniappan Kunal B. Karani Shaoling Huang David D. McPherson Christy K. Holland
author_sort	Himanshu Shekhar
title	In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke
title_short	In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke
title_full	In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke
title_fullStr	In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke
title_full_unstemmed	In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke
title_sort	in vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/d1579c4e74a347bc8589b30a95b120f9
work_keys_str_mv	AT himanshushekhar invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke AT roberttkleven invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke AT taopeng invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke AT arunkumarpalaniappan invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke AT kunalbkarani invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke AT shaolinghuang invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke AT daviddmcpherson invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke AT christykholland invitrocharacterizationofsonothrombolysisandechocontrastagentstotreatischemicstroke
_version_	1718387841070792704

In vitro characterization of sonothrombolysis and echocontrast agents to treat ischemic stroke

Ejemplares similares